The proposed research project will investigate the process by which mammalian growth is controlled by homocysteine derivatives, including homocysteic acid and complexes of homocysteine with pyridoxal, retinal, fatty aldehydes, and polyamine aldehydes. The key aspects of the growth process to be studied are the macromolecular changes produced by homocysteine and sulfate in the proteoglycans synthesized by cultured connective tissue cells, transformed cells, and malignant cells, the function of these homocysteine derivatives in the metabolic conversion of methionine to sulfate ester and other products, the relationship of sulfation of proteoglycans to contact inhibition in cultured cells, the effect of homocysteine derivatives on the growth of transplanted mouse adenocarcinoma, and the metabolic and macromolecular changes by which homocysteinemia produces accelerated arteriosclerosis. BIBLIOGRAPHIC REFERENCES: K.S. McCully, Homocysteine Thiolactone Metabolism in Malignant Cells; Cancer Research 36 (1976) 3198-3202. P. Clopath and K.S. McCully, Synthesis of Homolanthionine Sulfone and Homolanthione Sulfoxide; Analytical Biochemistry 73 (1976) 231-235.